From corn to cattle, gene editing is about to supercharge agriculture

Agriculture has come a long way in the past century. We produce more food than ever before -- but our current model is unsustainable, and as the world’s population rapidly approaches the 8 billion mark, modern food production methods will need a radical transformation if they're going to keep up. But luckily, there’s a range of new technologies that might make it possible. In this series, we’ll explore some of the innovative new solutions that farmers, scientists, and entrepreneurs are working on to make sure that nobody goes hungry in our increasingly crowded world.

Corn isn't the sexiest crop but it’s one of the most important. It’s the most abundant grain on Earth, used as food and biofuel around the globe. In ancient times, Mesoamericans thrived on it, waged wars over it. Their myths claimed corn was the matter from which gods created mankind itself.

But, just as corn helped create these civilizations, these civilizations helped create corn through meticulous selective breeding. Today’s grain hardly resembles its ancestors. Compared to the wild plant first cultivated by ancient Mexicans some ten thousand years ago, modern corn is a super mutant.

And yet, after all those thousands of years of cultivation, just two main genes are thought to be responsible for the evolution of the corn we eat today. Selective breeding is painstakingly slow and imprecise.

But that’s all about to change.

Selective breeding is painstakingly slow and imprecise. But that’s all about to change.

New gene editing tools like CRISPR/Cas9 now let scientists hack into genomes, make precise incisions, and insert desired traits into plants and animals. We’ll soon have corn with higher crop yields, mushrooms that don’t brown, pigs with more meat on the bone, and disease resistant cattle. Changes that took years, decades, or even centuries, can now be made in a matter of months. In the next five years you might eat tortilla chips made from edited corn. By 2020 you might drink milk from an edited cow.

Dubbed the "CRISPR Revolution" these scientific advances in gene editing have huge potential that many experts think could help fortify our food system and feed an increasing population of farmers who are threatened by food scarcity caused, in part, by climate change.

But not everyone is so certain. Beyond the contentious legal battles that have thus far complicated CRISPR science, calling into question who can and can't use the technology, some consumer rights advocates think these tools will be used to maintain the status quo of an industry based primarily on corporate profit. Meanwhile, residual worry about genetically modified organisms (GMOs) may influence the public perception of gene-edited organisms, steering consumers towards the "organic" aisle despite scientific evidence.

What is gene editing?

Gene editing is, simply put, the act of making intentional changes to DNA in order to create an organism with a specific trait or traits. It's like using a word processor to edit the words in a sentence. Geneticists insist we don't confuse this with genetic modification (otherwise called genetic engineering), which introduces new genes from different species in order to achieve desired traits. The difference may sound trivial but experts say it could help calm the concerns associated with GMOs.

Consider this simplification. We have the sentence, "The cat has a hat," but want to be more descriptive about the hat's color. With modification, we would borrow the German word for black and write, "The cat has a schwarz hat." The sentence makes sense (sort of) but it's obvious that to some people it would be problematic and maybe even an improper use of language. With editing, we don't have to borrow a word from another language. We instead just insert the English word and write, "The cat has a black hat."

"In the older, more traditional system, scientists were taking a gene from one species and putting it into a plant to confer a particular trait on that plant,” Rachel Haurwitz, co-founder of Caribou Biosciences, told Digital Trends. "That’s not what we’re looking to do. We’re looking to use CRISPR gene editing to achieve the same outcome as we can get from traditional breeding, just faster.”

This ability to edit with such speed and precision is still relatively new, and due largely to CRISPR, which emerged straight from nature to become the most popular and powerful gene editing tool used today. Discovered in bacteria in the late eighties, it wasn’t until 2005 that researchers began to unravel its role. Scientists found that when certain bacteria come under attack from viruses, they use special enzymes to cut, copy, and save a bit of the viral DNA. Later, if the intruder returns, the bacteria can quickly recognize it and react to defend itself.

A few years later, researchers realized this system could be used to cut and edit the DNA of any organism, not just viruses'. In 2012, Jennifer Doudna and Emmanuelle Charpentier published the first paper demonstrating how CRISPR can be used to edit an organism’s genome.

"We’re looking to use CRISPR gene editing to achieve the same outcome as we can get from traditional breeding, just faster."

Not only is this technique far cheaper, faster, and more precise than conventional genetic modification, it avoids many (if not all) of the issues raised by skeptics, whose main concerns point toward the creation of "transgenic" organisms.

But, whereas genetic modification entails combining DNA from multiple species, gene editing entails altering the DNA of one species with a trait that already exists naturally.

"Gene editing is not at all about taking DNA from a foreign species and integrating it into a plant,” Haurwitz said. “It’s really about working within the constraints of the plant’s own genome.”

Just over four years ago, Haurwitz founded Caribou as a spin off from Doudna’s lab at the University of California, Berkeley. Since then, her team has partnered with companies around the world, providing licensing rights to use the startup’s version of the gene editing tool. One of those partnerships may see the first CRISPR-edited organism come to market via DuPont Pioneer, one of the world's biggest chemical companies.

Crops

The day before Halloween 2015, Yinong Yang submitted an “Am I Regulated” letter to the United States Department of Agriculture's (USDA) Animal and Plant Health Inspection Service (APHIS). He and his colleagues at Penn State had used CRISPR to knock out a gene in white button mushrooms that makes them go brown over time. Without the browning gene, white buttons look better and last longer, and Yang wanted to know whether his mushrooms could legally go to market.

The following spring, the department’s response resonated throughout the scientific and agricultural community. “APHIS does not consider CRISPR/Cas9-edited white button mushrooms…to be regulated,” it wrote in an open letter.

Last year, researchers at DuPont Pioneer, the agriculture branch of the multi-billion-dollar conglomerate DuPont, published a study about a strain of corn engineered with CRISPR to be more resistant to drought. It’s one of several CRISPR-modified crops that may soon be coming to market.

It was a landmark decision. Yang's mushrooms were the first gene-edited crop cleared for commercial sale by the USDA, which made a clear distinction between genetic modification and gene editing, and set a precedent for those to come.

A few days later, DuPont -- the fourth largest chemical corporation in the world — received a similar response from the USDA regarding its CRISPR-edited waxy corn that’s disease resistant and drought tolerant. DuPont wasted no time announcing plans to take its crop to market within the next five to ten years.

“The USDA has said these products do not fall into their remit, as their remit is really focused on, say, plant pathogens or noxious weeds,” said Haurwitz, whose company provides DuPont with its CRISPR technology. “At the same time we’re seeing the FDA put out a call for information as they’re looking at their own remit to oversee the entire food supply, not just products made with modern biotechnology. And I think they’re looking to members of the scientific and business communities to really weigh in over the next few months."

Unlike most Button mushrooms, these ones don’t brown or develop blemishes from being handled. This trait doesn’t occur naturally — it happens because the gene that makes the mushrooms turn brown was selectively removed from them via the CRISPR/Cas9 method. (Photo: Yang Lab)

For Yang's part, he intends to improve his mushrooms before making them commercially available. Although not legally required, he plans to seek approval from the Food and Drug Administration (FDA) and Environmental Protection Agency (EPA).

Edited waxy corn may find its way into the food system much sooner than white button mushrooms, if not as human food than as fodder for the growing number of livestock around the world. Meanwhile, these livestock are also undergoing genetic edits as researchers use the same tools to make animals healthier, meatier, and more productive.

Livestock

Pigs harbor a lot of diseases and there are few as bad as porcine reproductive and respiratory syndrome (PRRS). It causes pregnant mothers to miscarry and makes it difficult for piglets to breathe. It’s a problem for the pig farmers as well. Every year, the PRRS virus costs the industry nearly $1.6 billion dollars in Europe and another $664 million in the US.

"The impacts of the disease for producers are often devastating,” said Jonathan Lightner, Chief Scientific Officer at biotech company Genus. "And the impacts on the animals themselves are terrible.”

“If we could integrate the polled phenotype into the dairy system, that would eliminate dehorning for at least seven or eight million animals a year.”

But Lightner and his team are working on a solution. In December 2015, scientists at Genus and the University of Edinburgh's Roslin Institute demonstrated how CRISPR could remove the CD163 molecule, a pathway through which the PRRS virus infects pig. Just last month, the researchers refined their work to remove just the portion of the gene that directly interacts with the virus. Lab tests, as published in a paper in the journal PLOS Pathogens, have shown that DNA in cells removed from these pigs successfully resist the virus. Next steps in the study will test whether the pigs themselves are resistant to the virus.

Swine are also the subject of research at Seoul National University in South Korea, where scientists led by Jin-Soo Kin are using a different gene-editing tool called TALEN to create meatier, “double muscle” pigs by removing a gene that inhibits muscle growth. “We could do this through breeding,” Kin told Nature back in 2015, “but then it would take decades.”

In fact, farmers have developed similar traits through breeding Belgian Blues, a type super-sculpted beef cattle prized for its lean meat and beefy build. It took over a hundred years to establish those traits in the breed.

Researchers at University of California, Davis and a startup called Recombinetics are using the same TALEN gene editing technique to cut decades down to days, removing the horned gene from common dairy cows and inserting the one that makes Angus beef cattle naturally dehorned or “polled.” Polled cattle are desirable because they pose less threat to their handlers and to each other. But, as Tad Sonstegard, Chief Science Officer of Acceligen (a Recombinetics subsidiary) explained, polled cattle in certain breeds are simply less productive.

Gene editing ala CRISPR/Cas9 has allowed scientists to not only produce polled (hornless) cows, but also cows that are immune to common diseases, such as tuberculosis. (Photo: Gregory Urquiaga/UC Davis)

"The issue is that the top [dairy] bulls that everyone wants are horned," Sonstegard said. "The animals that are polled that already exist have a difference of about $250 over their lifetime. If you’re running a thousand head dairy [operation], that’s a lot of money.”

What many ranchers do instead is dehorn their cattle, a stressful practice when anesthesia is used, a painful practice when it isn't, and a significant expense for the ranchers either way.

"If we could integrate the polled phenotype into the dairy system, that would eliminate dehorning for at least seven or eight million animals a year,” Sonstegard said. "If you include beef, that's up to fifteen million.”

Recombinetics has already bred a couple gene-edited calves, which are undergoing care and monitoring at UC Davis. But, before any gene-edited cows produce the milk in our grocery stores, Sonstegard said scientists would need to prove that milk from these cows is similar to horned and polled cows that haven't been gene edited. "That would be simple though," he said, "it would turn out the same."

Saving species

As the global population grows, so does the demand for food. Meanwhile, farmers around the world face food scarcity generated in part by a changing climate that makes caring for plants and livestock an increasingly difficult task.

But CRISPR-like tools may be able to help.

“On the plant side we’re looking at ways to breed plants that are more drought tolerant or in other ways can better survive the stresses of climate change,” Haurwitz said. "I think that’s incredibly valuable and important as we look at the exploding global population.” Caribou has also partnered with Genus in its project to breed PRRS virus resistant pigs.

Beyond his work at Recombinetics, Sonstegard sits on the scientific advisory board of the Centre for Tropical Livestock Genetics and Health, a Gates Foundation-backed initiative to improve the genetics of native livestock in tropical regions. Most productive livestock breeds can’t survive the heat or diseases present in tropical environments, and breeds native to tropical environments haven’t had the same selective breeding programs that generate highly productive livestock.

"Will CRISPR be used primarily for patenting foods in ways that fit in existing corporate profit models?"

"Most of the indigenous animals have not been under strict artificial selection,” Sonstegard said. "It’s all been done anecdotally, since most farmers don’t have that many cows and their systems aren’t that big." Meanwhile, most of the new DNA introduced to these herds is left over semen from bulls in developed countries, according to Sonstegard. "It’s cheap," he said, "and no one in the developed country wants it anymore, so they ship it overseas.”

There are a couple possible approaches to strengthening these indigenous breeds. One way would be to edit the DNA of bulls from productive breeds so that they’re more temperature tolerant and disease resistant within tropical climates. Those bulls could then be introduced to the native herds to reproduce and spread their productive genes. Alternatively, the DNA of indigenous bulls could be edited with genes likely to improve productivity of the herd, including milk production and carcass yield.

"Right now the trend in those countries is that there’s a linear growth in livestock numbers," Sonstegard said, "because they’re not improving production but demand is increasing, so they just make more animals.That’s not sustainable.”

Geneticist Tad Sonstegard analyzes BovineSNP50 BeadChips for genotypic data that decodes each animal’s genome at more than 50,000 locations. This type of data is used in cattle research ranging from genome selection to mapping of congenital defects. (Photo: USDA/Peggy Greb)

UC Davis geneticist Alison Van Eenennaam, who collaborates with Recombinetics on gene-editing polled cows, is absolutely optimistic about the tool -- “I think it can be used for very useful things,” she said. "Rather than ask ‘why’ we should use, let’s ask ‘how.’" -- but she’s also careful not to overstate the potential of gene editing. When asked whether the technology could be used to address world hunger, she said, "I kind of think that idea is polyamorous. Show me anything that can magically solve world hunger. Let’s not oversell this technology. It’s useful but it’s useful for a fairly discreet purpose at this stage, which is making edits to a [gene] sequence that we know has a particular effect.”

And CRISPR, of course, has it's skeptics. Stacy Malkan, Co-Director of U.S. Right to Know, a nonprofit that calls for transparency and accountability in the food system, is both concerned about the inherent risk involved in gene editing and suspects it could ultimately perpetuate an already imbalanced food system.

"Will CRISPR be used primarily for the purpose of patenting foods in ways that fit in existing corporate profit models,” she asked, "for example, to engineer commodity crops to withstand herbicides, or to engineer livestock to fit better in unhealthy confined feeding operations? Or will it be used to engineer foods that have consumer benefits? Will there be labeling, and safety assessments? There are many questions. Right now we hear a lot of marketing hype about possible benefits of CRISPR, but we heard the same promises about first-generation GMOs for decades and most of those benefits have not panned out.”

For scientists like Van Eenennaam, the GMO discussion is over. ""Frankly," she said, "I'm over the debate. If someone isn't convinced by the evidence that every single major scientific society in the world says it’s safe, than nothing I’m going to say is going to convince them any differently." When it comes to gene-edited organisms, most scientists are even more insistent about its safety. "There’s really no big difference between [gene editing] and conventional breeding," Van Eenennaam added.

But there isn't complete consensus. Malkan points to an interview she recently had with Michael Hansen, senior scientist from Consumers Union, in which Hansen said of CRISPR-like gene editing tools, "These methods are more precise than the old methods, but there can still be off-target and unintended effects. When you alter the genetics of living things they don’t always behave as you expect. This is why it’s crucial to thoroughly study health and environmental impacts, but these studies aren’t required."

Still, Malkan and others have their reservations, grounded in the idea that it's too early to determine the side effects. "CRISPR is a powerful research tool for helping scientists understand genetics, how cells react, how entire plants and systems react,” she said. "In my view these experimental technologies should be kept in the lab, not unleashed in our food system, until those systems are better understood."